AbstractBackgroundOur study aimed to characterize kidney retransplant recipients using an unsupervised machine‐learning approach.MethodsWe performed consensus cluster analysis based on the recipient‐, donor‐, and transplant‐related characteristics in 17 443 kidney retransplant recipients in the OPTN/UNOS database from 2010 to 2019. We identified each cluster's key characteristics using the standardized mean difference of >.3. We compared the posttransplant outcomes, including death‐censored graft failure and patient death among the assigned clustersResultsConsensus cluster analysis identified three distinct clusters of kidney retransplant recipients. Cluster 1 recipients were predominantly white and were less sensitized. They were most likely to receive a living donor kidney transplant and more likely to be preemptive (30%) or need ≤1 year of dialysis (32%). In contrast, cluster 2 recipients were the most sensitized (median PRA 95%). They were more likely to have been on dialysis >1 year, and receive a nationally allocated, low HLA mismatch, standard KDPI deceased donor kidney. Recipients in cluster 3 were more likely to be minorities (37% Black; 15% Hispanic). They were moderately sensitized with a median PRA of 87% and were also most likely to have been on dialysis >1 year. They received locally allocated high HLA mismatch kidneys from standard KDPI deceased donors. Thymoglobulin was the most commonly used induction agent for all three clusters. Cluster 1 had the most favorable patient and graft survival, while cluster 3 had the worst patient and graft survival.ConclusionThe use of an unsupervised machine learning approach characterized kidney retransplant recipients into three clinically distinct clusters with differing posttransplant outcomes. Recipients with moderate allosensitization, such as those represented in cluster 3, are perhaps more disadvantaged in the kidney retransplantation process. Potential opportunities for improvement specific to these re‐transplant recipients include working to improve opportunities to improve access to living donor kidney transplantation, living donor paired exchange and identifying strategies for better HLA matching.
Clinical Phenotypes of Dual Kidney Transplant Recipients in the United States as Identified through Machine Learning Consensus Clustering
Background and Objectives: Our study aimed to cluster dual kidney transplant recipients using an unsupervised machine learning approach to characterize donors and recipients better and to compare the survival outcomes across these various clusters. Materials and Methods: We performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in 2821 dual kidney transplant recipients from 2010 to 2019 in the OPTN/UNOS database. We determined the important characteristics of each assigned cluster and compared the post-transplant outcomes between clusters. Results: Two clinically distinct clusters were identified by consensus cluster analysis. Cluster 1 patients was characterized by younger patients (mean recipient age 49 ± 13 years) who received dual kidney transplant from pediatric (mean donor age 3 ± 8 years) non-expanded criteria deceased donor (100% non-ECD). In contrast, Cluster 2 patients were characterized by older patients (mean recipient age 63 ± 9 years) who received dual kidney transplant from adult (mean donor age 59 ± 11 years) donor with high kidney donor profile index (KDPI) score (59% had KDPI ≥ 85). Cluster 1 had higher patient survival (98.0% vs. 94.6% at 1 year, and 92.1% vs. 76.3% at 5 years), and lower acute rejection (4.2% vs. 6.1% within 1 year), when compared to cluster 2. Death-censored graft survival was comparable between two groups (93.5% vs. 94.9% at 1 year, and 89.2% vs. 84.8% at 5 years). Conclusions: In summary, DKT in the United States remains uncommon. Two clusters, based on specific recipient and donor characteristics, were identified through an unsupervised machine learning approach. Despite varying differences in donor and recipient age between the two clusters, death-censored graft survival was excellent and comparable. Broader utilization of DKT from high KDPI kidneys and pediatric en bloc kidneys should be encouraged to better address the ongoing organ shortage.
Characteristics of Kidney Recipients of High Kidney Donor Profile Index Kidneys as Identified by Machine Learning Consensus Clustering
Journal of Personalized Medicine | December 2, 2022 | Volume: 12 | Issue: 12 | Pages: 1992
Background: Our study aimed to characterize kidney transplant recipients who received high kidney donor profile index (KDPI) kidneys using unsupervised machine learning approach. Methods: We used the OPTN/UNOS database from 2010 to 2019 to perform consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in 8935 kidney transplant recipients from deceased donors with KDPI ≥ 85%. We identified each cluster’s key characteristics using the standardized mean difference of >0.3. We compared the posttransplant outcomes among the assigned clusters. Results: Consensus cluster analysis identified 6 clinically distinct clusters of kidney transplant recipients from donors with high KDPI. Cluster 1 was characterized by young, black, hypertensive, non-diabetic patients who were on dialysis for more than 3 years before receiving kidney transplant from black donors; cluster 2 by elderly, white, non-diabetic patients who had preemptive kidney transplant or were on dialysis less than 3 years before receiving kidney transplant from older white donors; cluster 3 by young, non-diabetic, retransplant patients; cluster 4 by young, non-obese, non-diabetic patients who received dual kidney transplant from pediatric, black, non-hypertensive non-ECD deceased donors; cluster 5 by low number of HLA mismatch; cluster 6 by diabetes mellitus. Cluster 4 had the best patient survival, whereas cluster 3 had the worst patient survival. Cluster 2 had the best death-censored graft survival, whereas cluster 4 and cluster 3 had the worst death-censored graft survival at 1 and 5 years, respectively. Cluster 2 and cluster 4 had the best overall graft survival at 1 and 5 years, respectively, whereas cluster 3 had the worst overall graft survival. Conclusions: Unsupervised machine learning approach kidney transplant recipients from donors with high KDPI based on their pattern of clinical characteristics into 6 clinically distinct clusters.
Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation
Annals of Internal Medicine | July 4, 2022 | Volume: 175 | Issue: 8 | Pages: 1073-1082
Background: This study aimed to better characterize morbidly obese kidney transplant recipients, their clinical characteristics, and outcomes by using an unsupervised machine learning approach. Methods: Consensus cluster analysis was applied to OPTN/UNOS data from 2010 to 2019 based on recipient, donor, and transplant characteristics in kidney transplant recipients with a pre-transplant BMI ≥ 40 kg/m2. Key cluster characteristics were identified using the standardized mean difference. Post-transplant outcomes, including death-censored graft failure, patient death, and acute allograft rejection, were compared among the clusters. Results: Consensus clustering analysis identified 3204 kidney transplant recipients with a BMI ≥ 40 kg/m2. In this cohort, five clinically distinct clusters were identified. Cluster 1 recipients were predominantly white and non-sensitized, had a short dialysis time or were preemptive, and were more likely to receive living donor kidney transplants. Cluster 2 recipients were older and diabetic. They were likely to have been on dialysis >3 years and receive a standard KDPI deceased donor kidney. Cluster 3 recipients were young, black, and had kidney disease secondary to hypertension or glomerular disease. Cluster 3 recipients had >3 years of dialysis and received non-ECD, young, deceased donor kidney transplants with a KDPI < 85%. Cluster 4 recipients were diabetic with variable dialysis duration who either received non-ECD standard KDPI kidneys or living donor kidney transplants. Cluster 5 recipients were young retransplants that were sensitized. One-year patient survival in clusters 1, 2, 3, 4, and 5 was 98.0%, 94.4%, 98.5%, 98.7%, and 97%, and one-year death-censored graft survival was 98.1%, 93.0%, 96.1%, 98.8%, and 93.0%, respectively. Cluster 2 had the worst one-year patient survival. Clusters 2 and 5 had the worst one-year death-censored graft survival. Conclusions: With the application of unsupervised machine learning, variable post-transplant outcomes are observed among morbidly obese kidney transplant recipients. Recipients with earlier access to transplant and living donation show superior outcomes. Unexpectedly, reduced graft survival in cluster 3 recipients perhaps underscores socioeconomic access to post-transplant support and minorities being disadvantaged in access to preemptive and living donor transplants. Despite obesity-related concerns, one-year patient and graft survival were favorable in all clusters, and obesity itself should be reconsidered as a hard barrier to kidney transplantation.
Distinct Phenotypes of Kidney Transplant Recipients in the United States with Limited Functional Status as Identified through Machine Learning Consensus Clustering
Journal of Personalized Medicine | May 25, 2022 | Volume: 12 | Issue: 6 | Pages: 859
Background: There have been concerns regarding increased perioperative mortality, length of hospital stay, and rates of graft loss in kidney transplant recipients with functional limitations. The application of machine learning consensus clustering approach may provide a novel understanding of unique phenotypes of functionally limited kidney transplant recipients with distinct outcomes in order to identify strategies to improve outcomes. Methods: Consensus cluster analysis was performed based on recipient-, donor-, and transplant-related characteristics in 3205 functionally limited kidney transplant recipients (Karnofsky Performance Scale (KPS) < 40% at transplant) in the OPTN/UNOS database from 2010 to 2019. Each cluster’s key characteristics were identified using the standardized mean difference. Posttransplant outcomes, including death-censored graft failure, patient death, and acute allograft rejection were compared among the clusters Results: Consensus cluster analysis identified two distinct clusters that best represented the clinical characteristics of kidney transplant recipients with limited functional status prior to transplant. Cluster 1 patients were older in age and were more likely to receive deceased donor kidney transplant with a higher number of HLA mismatches. In contrast, cluster 2 patients were younger, had shorter dialysis duration, were more likely to be retransplants, and were more likely to receive living donor kidney transplants from HLA mismatched donors. As such, cluster 2 recipients had a higher PRA, less cold ischemia time, and lower proportion of machine-perfused kidneys. Despite having a low KPS, 5-year patient survival was 79.1 and 83.9% for clusters 1 and 2; 5-year death-censored graft survival was 86.9 and 91.9%. Cluster 1 had lower death-censored graft survival and patient survival but higher acute rejection, compared to cluster 2. Conclusion: Our study used an unsupervised machine learning approach to characterize kidney transplant recipients with limited functional status into two clinically distinct clusters with differing posttransplant outcomes.
Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes
JAMA Surgery | May 4, 2022 | Volume: 157 | Issue: 7 | Pages: e221286
Abstract Background Based on expert opinion, solid organ transplant recipients from donors with bacteremia are treated with 7-14 days of pre-emptive antibiotic therapy (PAT). However, studies addressing necessity, optimal duration of therapy, and outcomes in kidney transplant recipients (KTR) are lacking. Methods We retrospectively reviewed all kidney transplants performed at our institution from 01/01/2015-01/01/2021 to identify those cases where matched deceased donors had positive blood cultures. Bacteremia was defined per CDC criteria. We analyzed rate of infection in the KTR with the same organism identified in the donor blood culture within 30 days of transplantation. Results A total of 56 KTRs with donor positive blood cultures were identified. Demographic data are summarized in Table 1. Twenty of 56 cases (35.8%) had bacteremia and 36 (64.2%) had organisms classified as common commensals. The most common organisms in the bacteremia group were Gram-negative bacteria (12/20) and Staphylococcus aureus (6/20). Most common commensals were coagulase-negative staphylococci (26/36) (Table 2). All KTR received preoperative antibiotics at the time of transplantation, primarily cefazolin (15/20), and vast majority received TMP/SMX prophylaxis, for Pneumocystis jirovecii, post-transplant (19/20). PAT was administered in 70% (14/20) cases of bacteremia for a median of 8.5 days (IQR 7-14), while six cases were left untreated (Table 2). In contrast, majority of cases with common commensals were not treated (75%, 27/36). Of the cases treated (9/36), median duration of therapy was 7 days (IQR 5-14). No cases of infection with the same organism identified in the donor blood culture were reported in KTR within 30 days of transplantation. Conclusion KTR donors with bacteremia who were treated received a median of 8.5 days of PAT with no instances of breakthrough infection. In contrast, majority of donor blood cultures with organisms classified as common commensals were not treated and did well. Future studies are needed to assess whether perioperative antibiotics coupled with TMP/SMX prophylaxis post-transplantation are sufficient in select cases of transplantation from donors with bacteremia. Disclosures All Authors: No reported disclosures
Clinically Distinct Subtypes of Acute Kidney Injury on Hospital Admission Identified by Machine Learning Consensus Clustering
Medical Sciences | September 27, 2021 | Volume: 9 | Issue: 4 | Pages: 60
Background: We aimed to cluster patients with acute kidney injury at hospital admission into clinically distinct subtypes using an unsupervised machine learning approach and assess the mortality risk among the distinct clusters. Methods: We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 4289 hospitalized adult patients with acute kidney injury at admission. The standardized difference of each variable was calculated to identify each cluster’s key features. We assessed the association of each acute kidney injury cluster with hospital and one-year mortality. Results: Consensus clustering analysis identified four distinct clusters. There were 1201 (28%) patients in cluster 1, 1396 (33%) patients in cluster 2, 1191 (28%) patients in cluster 3, and 501 (12%) patients in cluster 4. Cluster 1 patients were the youngest and had the least comorbidities. Cluster 2 and cluster 3 patients were older and had lower baseline kidney function. Cluster 2 patients had lower serum bicarbonate, strong ion difference, and hemoglobin, but higher serum chloride, whereas cluster 3 patients had lower serum chloride but higher serum bicarbonate and strong ion difference. Cluster 4 patients were younger and more likely to be admitted for genitourinary disease and infectious disease but less likely to be admitted for cardiovascular disease. Cluster 4 patients also had more severe acute kidney injury, lower serum sodium, serum chloride, and serum bicarbonate, but higher serum potassium and anion gap. Cluster 2, 3, and 4 patients had significantly higher hospital and one-year mortality than cluster 1 patients (p < 0.001). Conclusion: Our study demonstrated using machine learning consensus clustering analysis to characterize a heterogeneous cohort of patients with acute kidney injury on hospital admission into four clinically distinct clusters with different associated mortality risks.
Machine Learning Consensus Clustering of Hospitalized Patients with Admission Hyponatremia
Background: The objective of this study was to characterize patients with hyponatremia at hospital admission into clusters using an unsupervised machine learning approach, and to evaluate the short- and long-term mortality risk among these distinct clusters. Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,099 hospitalized adult hyponatremia patients with an admission serum sodium below 135 mEq/L. The standardized mean difference was utilized to identify each cluster’s key features. We assessed the association of each hyponatremia cluster with hospital and one-year mortality using logistic and Cox proportional hazard analysis, respectively. Results: There were three distinct clusters of hyponatremia patients: 2033 (18%) in cluster 1, 3064 (28%) in cluster 2, and 6002 (54%) in cluster 3. Among these three distinct clusters, clusters 3 patients were the youngest, had lowest comorbidity burden, and highest kidney function. Cluster 1 patients were more likely to be admitted for genitourinary disease, and have diabetes and end-stage kidney disease. Cluster 1 patients had the lowest kidney function, serum bicarbonate, and hemoglobin, but highest serum potassium and prevalence of acute kidney injury. In contrast, cluster 2 patients were the oldest and were more likely to be admitted for respiratory disease, have coronary artery disease, congestive heart failure, stroke, and chronic obstructive pulmonary disease. Cluster 2 patients had lowest serum sodium and serum chloride, but highest serum bicarbonate. Cluster 1 patients had the highest hospital mortality and one-year mortality, followed by cluster 2 and cluster 3, respectively. Conclusion: We identified three clinically distinct phenotypes with differing mortality risks in a heterogeneous cohort of hospitalized hyponatremic patients using an unsupervised machine learning approach.